Various organo-chemical methods can be used to produce peptides (see survey: WUNSCH, E. (1974) Synthesis of Peptides, in HOUBEN-WEYL, vol. 15, 1/2, Methoden der organischen Chemie, Muller, E. (editor) Georg Thieme Verlag, Stuttgart). Frequently, undesired side reactions are observed in the course of chemical peptide syntheses which reduce the yield and necessitate difficult and prolonged purifying processes. A particularly serious disadvantage of the traditional methods is the unsolved problem of racemization, which occurs especially in segment condensation by means of chemical bonding methods. Since stereoisomers can hardly be completely separated and the optical purity of the synthetics is a necessary prerequisite for their biological activity, the industrial synthesis of peptides by means of organo-chemical methods has considerable disadvantages. Moreover, in all chemical peptide-synthetic operations the tertiary functions of amino-acid structural elements must be masked reversibly because of the risk of side reactions.
The use of biocatalysts for the catalysis of the peptide linking step is available for avoiding the problems described above (see surveys: Jakubke, H. D. (1987) in S. Udenfriend, J. Meienhofer (eds.): The Peptides: Analysis, Synthesis, Biology, vol. 9, Academic New York, pp. 103-165; Kullmann (1987) Enzymatic Peptide Synthesis, CRC, Boca Raton, U.S.A.; Jakubke, H. D., Kuhl, P. and Konnecke, A. (1985) Angew. Chem. 97, 79). Chiral integrity remains preserved because of the stereospecificity of the proteases used as biocatalysts and the high degree of reaction control generally makes it possible to do without the protection of tertiary functions. The kinetically controlled path of the reaction plays a key part within the framework of enzyme-catalyzed peptide synthesis (Schellenberger, V., Jakubke, D. D. (1991) Angew. Chem. 103, 1440). The hydrolysis of the acyl enzyme intermediate, which accompanies formation of the peptide product in this method, and other possible proteolytic splittings, also constitute a problem for many synthetic reactions in that the yield of peptide product remains limited and the separation of by-products renders production more difficult.